Ayudando a los pacientes con cáncer

Sin resume

Murine models to investigate the influence of diabetic metabolism on the development of atherosclerosis and restenosis

This is an, un-copyedited, author manuscript that has been accepted for publication in the Frontiers in BioscienceAtherosclerosis and related forms of cardiovascular disease (CVD) are associated with several genetic and environmental risk factors, including hypercholesterolemia, diabetes mellitus (DM), hypertension, obesity and smoking. Human DM is a multisystem disorder that results from progressive failure of insulin production and insulin resistance. Most diabetic patients die from complications of atherosclerosis and CVD, and DM is also associated with increased risk of restenosis post-angioplasty. Furthermore, the incidence of DM, particularly type 2-DM, is expected to increase significantly during the next decades owing to the unhealthy effects of modern life-style habits (e.g., obesity and lack of physical exercise). Thus, it is of utmost importance to develop novel preventive and therapeutic strategies to reduce the social and health-care burden of CVD and DM. Although a number of physiological alterations thought to promote atherosclerosis have been identified in diabetic patients, the precise molecular mechanisms that link DM and atherosclerosis are largely unknown. Thus, the aim of this review is to discuss current murine models of combined DM and atherosclerosis and to explore how these experimental systems are being utilized to gain mechanistic insights into diabetes-induced neointimal lesion development, as well as their potential use in evaluating the efficacy of new therapies. Our discussion includes models generated by streptozotocin treatment and those resulting from naturally occurring or targeted mutations in the mouse.Work in the laboratory of the authors is supported by grants from the Spanish Instituto de Salud Carlos III (Red Temática de Investigación Cooperativa en Enfermedades Cardiovasculares RECAVA, Red de Grupos G03/212), and from the Spanish Ministry of Education and Science and the European Regional Development Fund (SAF2004-03057, SAF2005-06058). H. G.-N. is supported by an European Union Marie Curie postdoctoral fellowship.Peer reviewe

Fast regulation of AP-1 activity through interaction of lamin A/C, ERK1/2, and c-Fos at the nuclear envelope

Sequestration of c-Fos at the nuclear envelope (NE) through interaction with A-type lamins suppresses AP-1–dependent transcription. We show here that c-Fos accumulation within the extraction-resistant nuclear fraction (ERNF) and its interaction with lamin A are reduced and enhanced by gain-of and loss-of ERK1/2 activity, respectively. Moreover, hindering ERK1/2-dependent phosphorylation of c-Fos attenuates its release from the ERNF induced by serum and promotes its interaction with lamin A. Accordingly, serum stimulation rapidly releases preexisting c-Fos from the NE via ERK1/2-dependent phosphorylation, leading to a fast activation of AP-1 before de novo c-Fos synthesis. Moreover, lamin A–null cells exhibit increased AP-1 activity and reduced levels of c-Fos phosphorylation. We also find that active ERK1/2 interacts with lamin A and colocalizes with c-Fos and A-type lamins at the NE. Thus, NE-bound ERK1/2 functions as a molecular switch for rapid mitogen-dependent AP-1 activation through phosphorylation-induced release of preexisting c-Fos from its inhibitory interaction with lamin A/C

Insulin Receptor Substrate-1 Expression Is Increased in Circulating Leukocytes of Patients with Acute Coronary Syndrome

The mechanisms underlying the increased risk of cardiovascular disease associated with diabetes mellitus (DM) are not fully defined. Insulin resistance in human metabolic syndrome patients is associated with decreased expression of the insulin receptor substrate-2- (Irs2-) AKT2 axis in mononuclear leukocytes (MLs). Moreover, acute coronary syndrome (ACS) has been linked through genome-wide association studies to the 2q36-q37.3 locus, which contains the Irs1 gene. Here, we investigated the expression of insulin-signaling pathway genes in MLs from patients with DM, ACS, and ACS plus DM. Quantitative real-time PCR expression studies showed no differences in the mRNA levels of Irs2, Akt2, and Akt1 among all patients. However, Irs1 mRNA expression was significantly increased in patients with ACS—diabetics and nondiabetics—compared with diabetic patients without ACS (P < .02 and P < .005, resp.). The present study reveals for the first time an association between increased Irs1 mRNA levels in MLs of patients with ACS which is not related to DM

Desarrollo y evolución del sector vinícola aragonés desde finales del siglo XIX: análisis empresarial de los mercados y la producción

Las empresas sector vitivinícola aragonés, empapadas de una amplísima tradición, son embajadoras del esfuerzo empresarial y la adaptación a los nuevos mercados. El sector ha venido sufriendo desde los últimos 150 años numerosos altibajos, poniendo a prueba la capacidad de las bodegas. El enfoque de este trabajo está orientado al estudio, desde un punto de vista histórico empresarial, del desarrollo y la evolución del sector vinícola aragonés desde el último tercio del siglo XIX. A través del mismo se somete a análisis cómo han afectado, plagas, guerras y las nuevas tecnologías a la producción, la superficie cultivada, producción y comercialización del vino, con especial énfasis en el giro hacia la calidad vivido en los últimos años

SkyFlow: heterogeneous streaming for skyline computation using FlowGraph and SYCL

The skyline is an optimization operator widely used for multi-criteria decision making. It allows minimizing an n-dimensional dataset into its smallest subset. In this work we present SkyFlow, the first heterogeneous CPU+GPU graph-based engine for skyline computation on a stream of data queries. Two data flow approaches, Coarse-grained and Fine-grained, have been proposed for different streaming scenarios. Coarse-grained aims to keep in parallel the computation of two queries using a hybrid solution with two state-of-the-art skyline algorithms: one optimized for CPU and another for GPU. We also propose a model to estimate at runtime the computation time of any arriving data query. This estimation is used by a heuristic to schedule the data query on the device queue in which it will finish earlier. On the other hand, Fine-grained splits one query computation between CPU and GPU. An experimental evaluation using as target architecture a heterogeneous system comprised of a multicore CPU and an integrated GPU for different streaming scenarios and datasets, reveals that our heterogeneous CPU+GPU approaches always outperform previous only-CPU and only-GPU state-of-the-art implementations up to 6.86×and 5.19×, respectively, and they fall below 6% of ideal peak performance at most. We also evaluate Coarse-grained vs Fine-Grained finding that each approach is better suited to different streaming scenarios.This work was partially supported by the Spanish projects PID2019-105396RB-I00, UMA18-FEDERJA-108 and P20-00395-R. // Funding for open access charge: Universidad de Málaga / CBUA

Evaluation of gridded rain‐gauge‐based precipitation datasets: impact of station density, spatial resolution, altitude gradient and climate

Gridded precipitation datasets have been developed for data assimilation and evaluation tasks of weather and climate models and for climate analyses. Gridded data uncertainty evaluation is crucial to understand the limitations and feasibility. The development of high‐resolution daily gridded precipitation datasets is desirable, but several factors need to be considered, namely rain gauge station availability, their spatial distribution, and orographic and climate characteristics of a study area. Quality assessment of gridded datasets can present difficulties when the influence of these factors is not thoroughly analysed. The main objective of this study was a detailed validation of precipitation grids based on four factors, that is, station density used for grid construction, grid spatial resolution, station altitude, and climate type. To this end, 18 grids were built using six spatial resolutions (0.01°, 0.025°, 0.05°, 0.1°, 0.2° and 0.4°) and three station densities (25, 50 and 75% of all available stations). Results indicate larger differences among the grids as a function of analysed factors. Station density was found to be the main factor, whereas grid spatial resolution had minor importance. However, the latter factor becomes more relevant in areas with strong altitude gradients and when a high station density is available. In addition, weak and moderate precipitation is overestimated on daily grids, whereas heavy precipitation cells are less frequent, reducing data variability. On the contrary, monthly and annual aggregates present less deviation from the observed distribution than daily comparisons. These findings question the applicability of the daily grid datasets for validation studies and climate analysis on a grid cell level.Funding came from projects LE240P18 (Consejería de Educación, Junta de Castilla y León) and CGL2016‐78702‐C2‐1‐R, PID2019‐108470RB‐C22, CGL2016‐80609‐R and PID2019‐108470RB‐C21 (Ministerio de Economía y Competitividad)

Pathophysiology of the proatherothrombotic state in the metabolic syndrome

15 pages, 1 figure.--PMID: 20036940 [PubMed]The metabolic syndrome (MetS) is defined by the presence of at least three of the following abnormalities: glucose intolerance, hypertension, abdominal obesity, low HDL-cholesterol levels and hypertriglyceridemia. Obesity and insulin resistance are very frequently associated to the MetS and play a pivotal role in the development of type 2 diabetes mellitus (T2DM), which in turn increases the risk of cardiovascular disease. Although it varies among ethnic groups, the worldwide prevalence of MetS is 23% in young adults and increases with age. Remarkably, the prevalence of MetS is expected to increase during the next decades due in part to the acquisition of unhealthy life-style habits (e.g., sedentarism, smoking, unhealthy diet, etc). A major pathological alteration present in the MetS is a prothrombotic state as a result of endothelial dysfunction and hypercoagulability produced by a dysbalance of coagulation factors and proteins involved in the regulation of fibrinolysis. Although intensive research in recent years has permitted the identification of a number of prothrombotic alterations in MetS patients, a better understanding of the molecular mechanisms underlying the relationship between MetS and atherotrombosis is required to improve preventive and therapeutic strategies. In this review we discuss the main alterations in the endothelial function, coagulation cascade, fibrinolysis and platelet function that promote atherothrombosis in MetS patients. We also review available mouse models exhibiting alterations in atherothrombosis.Work in the authors’ laboratories is supported by grants from the Spanish Ministry of Science and Innovation and the European Regional Development Fund (SAF2007-62110), Instituto de Salud Carlos III (RECAVA grants RD06/0014/0004 and RD06/0014/0021), Generalitat Valenciana (GV/2007/164), Fundación Ramón Areces, Fina Biotech S.L., and Universidad de Talca (PIFRECV, Research Program of Cardiovascular Disease Risk).Peer reviewe

Sensorless unbalance correction as an ancillary service for LV 4-Wire/3-Phase power converters

IEEE Energy Conversion Congress and Exposition (9th. 2017. Cincinnati